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M R Stroud

Publications and source records attributed to M R Stroud.

At least 37 records · Page 2Linked to original sources

Human tumor-associated Le(a)-Le(x) hybrid carbohydrate antigen IV3(Gal beta 1-->3[Fuc alpha 1-->4]GlcNAc)III3FucnLc4 defined by monoclonal antibody 43-9F: enzymatic synthesis, structural characterization, and comparative reactivity with various antibodies.

Two Le(a)-cross-reacting monoclonal antibodies (mAbs) were previously established which define complex tumor-associated carbohydrate antigens. The first mAb, 43-9F, was raised against human squamous cell lung carcinoma and shows preferential reactivity with various human cancers over normal cells. Its tumor cell binding activity is best inhibited by a milk oligosaccharide characterized as Le(a)-Le(x) [Mårtensson, S., et al. (1988) Cancer Res. 48, 2125], Gal beta 1-->3[Fuc alpha 1-->4] GlcNAc beta 1-->3Gal beta 1-->4]Fuc alpha 1-->3]-GlcNAc beta 1-->3Gal beta 1-->4Glc (1). The second mAb, ST-421, was raised against human gastric cancer xenograft in nude mice and found to have strong tumor growth-suppressing activity in nude mice. The epitope recognized by ST-421 was chemically identified as Le(a)-Le(a), Gal beta 1-->3 [Fuc alpha 1-->4]GlcNAc beta 1-->3Gal beta 1-->3-[Fuc alpha 1-->4] GlcNAc beta 1-->3Gal beta 1-->4Glc (2) [Stroud, M.R., et al. (1991) J. Biol. Chem. 266, 8439]. Both 43-9F and ST-421 cross-react with Le(a). Identification of the 43-9F antigen as structure 1 (Le(a)-Le(x)) is tentative since it was not based on isolation and chemical characterization of antigen from tumor cells or tissues. We therefore synthesized structure 1 starting from sialyl-nor-hexaosylceramide (VI3NeuAcnLc6), with sequential enzymatic hydrolysis by sialidase and beta-galactosidase followed by addition of beta 1-->3Gal with beta 1-->3 galactosyltransferase. This yielded the hybrid type 1/type 2 chain core structure IV3-(Gal beta 1-->3GlcNAc)nLc4, which was fucosylated with alpha 1-->3/4 fucosyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Further studies on cell adhesion based on Le(x)-Le(x) interaction, with new approaches: embryoglycan aggregation of F9 teratocarcinoma cells, and adhesion of various tumour cells based on Le(x) expression.

We previously proposed specific interaction of Le(x) (Gal beta 1-->4 [Fuc alpha 1-->3]-GlcNAc beta 1-->3Gal) with Le(x) as a basis of cell adhesion in pre-implantation embryos and in aggregation of F9 teratocarcinoma cells, based on several lines of evidence (Eggens et al., J. Biol Chem (1989) 264:9476-9484). We now present additional evidence for this concept, based on autoaggregation studies of plastic beads coated with glycosphingolipids (GSLs) bearing Le(x) or other epitopes, and affinity chromatography on Le(x)-columns of multivalent lactofucopentaose III (Le(x) oligosaccharide) conjugated with lysyllysine. Comparative adhesion studies of Le(x)-expressing tumour cells vs their Le(x)-non-expressing variants showed that only Le(x)-expressing cells adhere to Le(x)-coated plates and are involved in tumour cell aggregation, in analogy to F9 cell aggregation. The major carrier of Le(x) determinant in F9 cells is not GSL but rather polylactosaminoglycan ('embryoglycan'), and we demonstrated autoaggregation of purified embryoglycan in the presence of Ca2+, and reversible dissociation in the absence of Ca2+ (addition of EDTA). Defucosylated embryoglycan did not show autoaggregation under the same conditions. Thus, Le(x)-Le(x) interaction has been demonstrated on a lactosaminoglycan basis as well as a GSL basis. A molecular model of Le(x)-Le(x) interaction based on minimum energy conformation with involvement of Ca2+ is presented.

Carbohydrate Sequence↗

The risk of small St. Jude aortic valve prostheses.

We reviewed our 12-year experience with 254 adult patients who had St. Jude valves in the aortic position and used multivariate analysis to examine risk factors possibly affecting long-term morbidity and mortality. Nineteen-millimeter or 21-mm valves were implanted in 115 patients. Poor preoperative congestive heart failure status was associated with persistent congestive heart failure on late follow-up. Preoperative congestive heart failure and coronary artery disease were the only predictors of overall late death. Late deaths associated with heart failure and late sudden deaths were examined separately. Preoperative degree of heart failure was the only predictor of late death with associated heart failure. The implantation of a 19- or 21-mm valve in patients with a body surface area greater than 1.9 m2 somewhat increased the risk of late sudden death. In patients with a body surface area greater than 1.9 m2 and with a 19-mm or 21-mm annulus, consideration should be given to using a high-performance St. Jude valve or performing an annulus-enlarging procedure if this can be done with negligible morbidity.

Adult↗

St. Jude prosthesis for aortic and mitral valve replacement: a ten-year experience.

From January 1, 1979 through December 1990, 456 adult patients underwent isolated aortic (AVR) (254) or mitral (MVR) (202) valve replacement with the St. Jude prosthesis at the Medical University of South Carolina. Age ranged from 21 to 84 years (mean: 54 +/- 15 years for AVR; 51 +/- 13 years for MVR). Male sex predominated in the AVR group (66%) and female sex in the MVR group (64%). Ninety-two patients (20%) had associated coronary artery bypass grafting (AVR, 25%; MVR, 14%). There were 17 deaths (3.7%) occurring during the same hospitalization or within 30 days (AVR, 10/254 [3.9%]; MVR, 7/202 [3.5%]). Follow-up is 94.5% complete and ranges from 1.0 to 131 months (mean, 55 +/- 37 months; total, 2,073 patient-years). In the AVR group, 53 late deaths have occurred and actuarial survival is 80% +/- 3% at 5 years and 47% +/- 9% at 10 years. Twenty-one patients have sustained thromboembolic episodes (1.8%/patient-year), and the probability of remaining free of thromboembolism at 10 years is 67% +/- 13%. The mean improvement in New York Heart Association functional class from preoperative to postoperative is 3.1 +/- 0.76 to 1.6 +/- 0.84 (p < 0.0001). In the MVR group, there have been 41 late deaths, and the actuarial survival was 80% +/- 3% at 5 years and 63% +/- 5% at 10 years. Twenty-eight patients have sustained thromboembolic complications (2.9%/patient-year), and the probability of remaining free of thromboembolism at 10 years is 77% +/- 5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve↗

Structural characterization of x2 glycosphingolipid, its extended form, and its sialosyl derivatives: accumulation associated with the rare blood group p phenotype.

It has been suggested that the x2 glycosphingolipid (GSL) could offer a structural basis for a P-like antigen activity found in blood group p individuals [Kannagi R., Fukuda, M.N., Hakomori, S. (1982) J. Biol. Chem. 257, 4438]. The structures of the x2 and sialosyl-x2 GSLs have been confirmed unequivocally as shown below by +FAB-MS, methylation analysis by GC-MS, and 1H-NMR. We have established a [formula: see text] monoclonal antibody (TH2) specific for the GalNAc beta 1----3Gal beta 1----4GlcNAc epitope, the terminal trisaccharide of x2 GSL. Application of MAb TH2 on TLC immunoblotting together with chemical analysis indicates the following points of interest: (i) the existence of extended type GSLs having the same x2 terminal structure; (ii) the chemical quantities of x2, sialosyl-x2, and extended x2 found in blood cells and in various tissues including carcinomas being nearly the same; (iii) considerably larger quantities of x2 and x2-derived structures found in blood samples of rare blood group p individuals. The accumulation of x2 and its derivatives in blood cells of p individuals is in contrast to the occurrence of these GSLs as extreme minor components in normal human red blood cells and tissues, and they may be responsible for the reported P-like activity in blood group p individuals [Naiki, M., & Marcus, D. M. (1977) J. Immunol. 119, 537].

ABO Blood-Group System↗

Specificity and immunobiological properties of monoclonal antibody IMH2, established after immunization with Le(b)/Le(a) glycosphingolipid, a novel extended type 1 chain antigen.

Extended lacto-series type 1 chain antigens lacking type 2 chain core have recently been shown to comprise a new type of tumor-associated carbohydrate antigen. Examples are Le(a)/Le(a) (IV3Gal beta 1----3[Fuc alpha 1----4]Glc-NAcLc4Cer) and Le(b)/Le(a) (IV3Fuc alpha 1----2Gal beta 1----3[Fuc alpha 1----4]Glc-NAcLc4Cer) (M. R. Stroud, et al., J. Biol. Chem., 266: 8439-8446, 1991; Eur. J. Biochem., 203: 577-586, 1992). We have now established an IgG3 mouse monoclonal antibody (IMH2) after immunization of mice with Le(b)/Le(a) antigen; however, monoclonal antibody (MAb) IMH2 reacted not only with the immunogen used but also with Le(y)/Le(x) and to a lesser degree with short-chain Le(y) or Le(b) with hexasaccharide ceramide (i.e., IV2FucIII3FucnLc4Cer or IV2FucIII4FucLc4Cer). It showed a high incidence of staining and strong reactivity with carcinomas of colon, rectum, liver, pancreas, and endometrium, but no reactivity with normal colonic mucosa at various loci, and minimal reactivity with normal liver, pancreas, or uterine endometrium. On the other hand, it reacted with normal gastric mucosa, cecal mucosa, urothelium, adrenal glands, and thymus. Its expression in colorectal tumors and normal cecal tissue was independent of secretor status, whereas that in normal urothelium was dependent on secretor status. MAb IMH2 displayed strong lymphocyte-activated or complement-dependent killing of human colonic cancer Colo205 cells in vitro, and inhibition of Colo205 growth in vivo; this inhibition was comparable to that by MAb NCC-ST-421, which is directed to Le(a)/Le(a) epitope (M. Watanabe, et al., Cancer Res., 51:2199, 1991). These results indicate that a new extended type 1 chain structure, Le(b)/Le(a), is a useful tumor marker associated with carcinomas of colon, rectum, pancreas, liver, and endometrium and that MAb IMH2 has potential diagnostic or therapeutic applicability for these carcinomas.

Animals↗

Extended type-1 chain glycosphingolipid antigens. Isolation and characterization of trifucosyl-Leb antigen (III4V4VI2Fuc3Lc6).

A Lewis-b-active glycosphingolipid containing a repetitive type-1 chain carbohydrate core was isolated from human colonic adenocarcinoma cell line Colo205. This glycosphingolipid was purified by HPLC and preparative high-performance thin-layer chromatography and its structure elucidated by positive-ion fast-atom-bombardment mass spectrometry with collision-induced disassociation, 1H-NMR spectroscopy and methylation analysis. The glycosphingolipid was found to be a trifucosylated derivative of this novel carbohydrate core, having the following structure: [formula; see text].

Adenocarcinoma↗

Selectin GMP-140 (CD62; PADGEM) binds to sialosyl-Le(a) and sialosyl-Le(x), and sulfated glycans modulate this binding.

GMP-140 (CD62; PADGEM) is a member of the selectin family expressed highly at the surface of platelets and endothelial cells by agonists such as thrombin or phorbol esters. Previous studies indicate that the lectin domain of GMP-140 recognizes sialosyl-Le(x) (SLex) and to a lesser extent Le(x) (Polley MJ, et al., Proc Natl Acad Sci USA 88:6224, 1991). We now report that GMP-140 binds to sialosyl Lea (SLea) and to SLex, and that degree of binding to SLea is greater than that to SLex under our experimental conditions. Binding of activated platelets to SLea or SLex was inhibited to various degrees in the presence of sulfated glycans, suggesting that sulfated glycans induce conformational change in the lectin domain of GMP-140 and modulates its binding affinity to SLea and SLex.

Antibodies, Monoclonal↗

Extended type 1 chain glycosphingolipids: dimeric Lea (III4V4Fuc2Lc6) as human tumor-associated antigen.

Glycolipid extracts from various human cancer tissues and cell lines showed the presence of a slow-migrating glycolipid component which was strongly reactive with monoclonal antibody (mAb) NCC-ST-421 (raised against human gastric adenocarcinoma) and weakly cross-reactive with anti-Lea mAbs. The slow-migrating glycolipid was isolated from human colonic adenocarcinoma cell line Colo205 grown in nude mice, and was purified by high-performance liquid chromatography followed by preparative thin-layer chromatography. Its structure was elucidated by sequential enzymatic degradation and thin-layer chromatography immunostaining of the degradation products with various mAbs, 1H NMR spectroscopy, positive-ion fast atom bombardment mass spectrometry, and methylation analysis. The major slow-migrating component reacting with mAb ST-421 was identified as dimeric Lea, with the structure as follows. [formula: see text] Antigens containing this structure and various analogous structures (including enzymatically synthesized Lea/Lex hybrid antigen) were tested with ST-421. While the mAb was equally reactive with dimeric Lea and Lea/Lex, only the former was chemically detectable as the slow-migrating glycolipid from the tumor extract. ST-421 showed less reactivity with simple Lea (III4FucLc4) or extended Lea (V4FucLc6, and/or IV3Gal beta 1----3[Fuc alpha 1----4]GlcNAcnLc4), and was not reactive with Lex/Lex (dimeric Lex). It was concluded, therefore, that the major tumor-associated slow-migrating glycolipid reacting with ST-421 has the dimeric Lea structure shown above. Since extension of lacto-series structure has been shown to be limited to type 2 chain in normal cells and tissues, extended elongation of type 1 chain as shown in this structure represents a novel tumor-associated epitope.

Adenocarcinoma↗

In vitro and in vivo antitumor effects of murine monoclonal antibody NCC-ST-421 reacting with dimeric Le(a) (Le(a)/Le(a)) epitope.

A murine monoclonal antibody (MAb), NCC-ST-421 (IgG3), was raised by using a human gastric cancer xenograft St-4 as immunogen. Immunization was achieved by transferring immunocompetent normal BALB/c mouse spleen cells into BALB/c-nu/nu mice bearing St-4 tumors. Hybridomas were produced from spleen cells of the mice after rejection of the tumors and were screened for preferential reactivity with cancers on formalin-fixed paraffin sections, as described previously for establishment of MAb NCC-ST-439 (M. Watanabe et al., Jpn. J. Cancer Res., 76: 43-52, 1985). The immunobiological and immunochemical properties of the new MAb NCC-ST-421 are described here. The MAb is essentially directed to a structure with dimeric Le(a) (V4III4Fuc2Lc6Cer) epitope (Gal beta 1----3[Fuc alpha 1----4]GlcNAc beta 1----3Gal beta 1----3[Fuc alpha 1----4]GlcNAc beta 1----3Gal beta 1----4Glc beta 1----1 Cer). It cross-reacts with Le(a) but does not show any effect on Le(a)-positive RBC in vitro or on Le(a)-positive tissue loci in vivo. ST-421 strongly induced antibody-dependent cellular cytotoxicity using human peripheral blood leukocytes as effector cells with a variety of human tumor cells, using the short-term 51Cr release assay. It also showed striking complement-dependent cytotoxicity with a human complement source and was able to produce lysis of a variety of human cancer cell lines, supporting its observed ability to cause cytotoxic suppression of tumor growth in nude mice. In another series of experiments, i.p. injection of ST-421 completely inhibited growth of human tumor xenografts in nu/nu mice, and this inhibitory activity was closely dependent on expression of the dimeric Le(a) antigen on the cell surface. While Le(a) antigen was expressed in the kidneys of nu/nu mice, infusion of ST-421 in these mice did not cause histological change in kidney tissue. This finding suggests that the MAb does not damage normal cells or tissues which contain cross-reacting Le(a) antigen. These results demonstrate that ST-421 exerts a significant antitumor effect in vitro as well as in vivo, does not affect Le(a) antigen expressed on normal tissues, and therefore has potential application in therapy of certain types of human cancer which express the dimeric Le(a) antigen.

Animals↗

Differentiation of type 1 and type 2 chain linkages of native glycosphingolipids by positive-ion fast-atom bombardment mass spectrometry with collision-induced dissociation and linked scanning.

Two underivatized glycosphingolipids, Le(b) and Le(y), isomeric in carbohydrate structure (Fuc alpha 1-->2Gal beta 1--> 3[Fuc alpha 1-->4]GlcNAc beta 1-->3Gal beta 1-->4Glc beta 1-->1Cer and Fuc alpha 1-->2Gal beta 1-->4[Fuc alpha 1-->3]GlcNAc beta 1-->3Gal beta 1--> 4Glc beta 1-->1Cer, respectively), were analyzed by positive-ion fast-atom bombardment (FAB) mass spectrometry with high energy collision-induced dissociation (CID) and linked scanning. The two isomers were distinguishable by the abundance of product ions derived from the non-reducing terminal tetrasaccharide fragment via sequential beta-eliminations of vicinally linked saccharide residues. Following earlier studies from other laboratories, which have dealt primarily with positive-ion FAB-CID mass spectrometry of simple model oligosaccharides, these results exemplify the practical application of two-sector methodology to underivatized complex glycoconjugates commonly encountered in the biomedical field.

Carbohydrate Conformation↗

Profiles of Lewisx-containing glycoproteins and glycolipids in sera of patients with adenocarcinoma.

Oligosaccharides with Lex determinant (Gal beta 1----4[Fuc alpha 1----3]GlcNAc) are accumulated in large quantities in various adenocarcinomas. Monoclonal antibodies recognizing mono-, di-, or trimeric Lex showed a preferential staining of specific stages of human fetal tissues and various human adenocarcinomas. Thus, these carbohydrate epitopes are typical of oncodevelopmental antigens. The present study investigated the presence of Lex epitope in sera of normal individuals and cancer patients, utilizing two high-affinity monoclonal antibodies, SH1 and SH2, directed to mono- and dimeric Lex structures, respectively. The Lex antigen in serum was eluted in the void volume fraction of a gel filtration column, determined by using monoclonal antibody SH1, and found to be carried on a glycoprotein with a molecular weight of approximately 200,000. The Lex antigen was present in the void volume fraction of the majority (85%) of sera from adenocarcinoma patients. Although the Lex epitope was also detected in a smaller proportion (33%) of normal sera, its levels were significantly lower than in cancer sera. Lex antigen was also detected in serum glycolipid fraction; however, no significant differences were observed in normal and cancer sera. A double determinant solid phase immunoassay utilizing SH2 as the capture antibody and SH1 as the detecting antibody allowed direct determination of Lex levels in sera. By the use of this direct assay, the levels of serum Lex were found to increase in association with the progression of colorectal cancer (Dukes A to D). The percentage of detectability in sera from colon cancer patients was as follows: Dukes A, 20%; Dukes B, 45%; Dukes C, 67%; and Dukes D, 74%. The levels of serum Lex were also of prognostic value in Dukes C cancer patients after surgery and during postoperative follow-up.

Adenocarcinoma↗

A comparison of endoesophageal tubes. Improved results with the Atkinson tube.

We reviewed our use of endoesophageal tubes for the palliation of patients with carcinoma of the esophagus from 1973 through 1986. Celestin tubes were implanted by means of laparotomy and traction. Proctor-Livingston tubes were implanted by pulsion with frequent laparotomy for staging. All Atkinson tubes were placed by means of the pulsion method without simultaneous laparotomy in any case. Patients with an Atkinson tube had fewer complications, including aspiration, sepsis, reflux, and pneumonia. Mean hospital stay was shortened to 4 days when the Atkinson tube was used, and hospital death rate was 6% versus 42% when either the Celestin or Proctor-Livingston tube was used. Mean long-term survival (108 days) was significantly lengthened when Atkinson tubes were used. A comparison of all patients receiving tubes revealed a less frequent prevalence of reflux when the distal end of the tube was positioned above the gastroesophageal junction. Laparotomy resulted in significantly more episodes of aspiration, sepsis, reflux, and pneumonia. Laparotomy was also associated with a 41% hospital death rate versus 17% when laparotomy was not performed. Hospital days were shortened to 7 versus 16 days when laparotomy was not performed. The Atkinson tube provided improved palliation and decreased morbidity and mortality in our hands. These benefits were probably the results of ease of insertion without the use of a laparotomy and the ability in most cases to position the distal end of the tube above the gastroesophageal junction.

Aged↗

A novel tumor-associated, developmentally regulated glycolipid antigen defined by monoclonal antibody ACFH-18.

A mouse IgM monoclonal antibody, ACFH-18, was established after immunization of mice with the human gastric cancer cell line MKN74. The antibody reacts strongly with gastrointestinal carcinoma and showed a clear dependence on the degree of differentiation of gastric cancer cells. The antibody defines a series of glycolipid species with extremely slow TLC mobility present in both acidic and neutral glycolipid fractions of the extract from gastrointestinal adenocarcinoma and the original MKN74 cells. Isolation and structural study of the active glycolipids present in the acidic and neutral fractions and comparison of the antibody reactivity with glycolipids having related structures revealed a novel specificity. The minimum requirement for the maximal reactivity of ACFH-18 was identified as VII3Fuc-nLc10 (Structure A below and Fig. 8 in text). Since the antibody did not react with III3Fuc-nLc6 (Structure B below), which shares the same terminal sequence as VII3Fuc-nLc10, and since it cross-reacted with VII3Fuc-nLc8 (Z1 glycolipid) and VII3Fuc,V3-Fuc,III3Fuc-nLc8 (Z3 glycolipid), antibody ACFH-18 is capable of recognizing a fucosyl residue plus an internal repeating N-acetyllactosamine proximal to ceramide, as indicated by lines in Fig. 8 (Structures A, B, and E-G). (Formula: see text).

Animals↗

Valve prostheses in children: a reassessment of anticoagulation.

We have previously published evidence that children with St. Jude Medical prostheses on the left side of the heart may not require anticoagulation. Between March 1979 and September 1986, we followed up 48 patients who had no anticoagulant therapy for up to 7 years after valve replacement, an aggregate of 122 patient-years. The 25 male and 23 female patients ranged in age at implantation from 5 months to 21 years (12 +/- 6 years, mean +/- standard deviation). Five patients (all with complex associated malformation) died in the hospital (10%), and nine died late (22%). None of the early and one of the late deaths was associated with a thrombosed prosthesis. During follow-up, seven thrombotic (one mitral, one aortic) or thromboembolic (two mitral, three aortic) events occurred (5.7 +/- 2.1 per 100 patient-years). Of these seven events, five occurred within the last 14 months of the study. There was no relation of these events to age of patient at implantation, age at the time of even, gender, or site of implantation. Concurrently, we have followed up 340 adult patients with St. Jude Medical prostheses who had warfarin sodium (Coumadin) anticoagulation for 875 patient-years. By the end of this study, the children who did not receive anticoagulants were significantly less free of thrombotic and thromboembolic events than the adults who did receive anticoagulants (p less than 0.01).

Anticoagulants↗

Criteria for selection of future physicians.

Academic achievement correlates poorly with clinical performance of physicians, so it is probably more important to select college students for medical school admission who will be superior physicians than to select those who will be excellent medical students. Before such selection criteria can be developed, a valid description of a superior physician must be determined. The relative importance of 87 characteristics of a superior physician, based on a previously published list, was determined by asking medical school faculty members to rate them. The resulting description of a superior physician is valid, because it correlated very highly (r = 0.87, p less than 0.001) with the published ratings of the same characteristics from decades earlier in another part of the country, and because it was constant across many subgroups. The faculty was also asked to rate how easily each characteristic could be taught, and those ratings were validated by high correlations across several subgroups. The importance and the teachability ratings were combined into a nonteachable-important index (NTII) that provides a rank order of traits that are important but cannot be taught easily. These are the characteristics that should be used in selecting future physicians.

Character↗

Trends and results in tricuspid valve surgery.

Forty-six tricuspid valve operations were performed over 12 years. Operations were conservative (two valvotomies, eight DeVega annuloplasties, seven Carpentier rings) in 17 and valve replacement (17 mechanicals, 12 tissues) in 29. Operative mortality rate was improved with better preoperative functional class, use of cardioplegia, or use of annuloplasty. Heart block occurred less with annuloplasty (6 vs 24 percent). Long-term survival was similar with annuloplasty or porcine valve replacement, but was poorer with mechanical valve replacement. Four of eight DeVega annuloplasties failed during the operative (two) or late (two) period. When the anatomy is suitable, we believe the Carpentier ring annuloplasty to be safe and effective. When valve replacement cannot be avoided, we believe replacement with a tissue valve is preferable.

Adolescent↗

A prospective randomized study of hydroxyethyl starch, albumin, and lactated Ringer's solution as priming fluid for cardiopulmonary bypass.

The ideal priming fluid for cardiopulmonary bypass is not known. We designed a study to determine whether there are important differences in the clinical effects of hydroxyethyl starch versus albumin when used in priming fluid, and in the clinical effects of colloid versus crystalloid priming fluid. We prospectively randomized 83 adult patients undergoing coronary artery bypass or valve replacement. All patients were managed by standardized protocol, and they received one of three priming fluids for bypass: hydroxyethyl starch (HES), 26 patients; albumin (ALB), 28 patients, and lactated Ringer's solution (LRS), 29 patients. The groups were stratified by body weight and type of operation. We measured 41 variables relating to operative time factors, fluid balance, bleeding, and organ function (renal, cardiac, and pulmonary) at several time intervals. The LRS group had a significantly lower colloid osmotic pressure than the other two groups, and the HES group had a substantially higher blood viscosity. Although the prothrombin time was significantly lower in the LRS group (p less than 0.05), the differences were very small and not clinically important. The platelet count in the HES group was significantly lower than in the other two groups immediately after bypass, but it was not different by the time the patients left the operating room. There were no differences among the groups in chest tube drainage, blood bank usage, or fluid balance. Postoperatively, the pulmonary shunt fraction was significantly greater in the LRS group. Body weight increased more in the LRS than in the HES and ALB groups (p = 0.01). No adverse reaction to the prime solutions was noted. The differences between the HES and ALB groups--prothrombin time, platelet count, and blood viscosity--had no apparent clinical effects; thus, the two may be considered clinically equivalent. The greater somatic and pulmonary fluid accumulation in the LRS group suggests that colloid is preferable to crystalloid in priming fluid.

Albumins↗